Divalent cations such as Mg.sup.2+ or Ca.sup.2+ are known to be important in modulating the binding affinity of hormones such as oxytocin (Di Scala-Guenot, D. et al., Biochem. J. 284:499-505, 1992; Pearlmutter, A. F. et al. J. Biol. Chem. 254:3899-3906 1979; Pliska, V., et al. Biochem. J. 277:97-101, 1991); vasopressin (Di Scala-Guenot, D. et al., 1992; Pearlmutter, A. F. et al., 1979; Altura, B. M. et al. Am. J. Physiol. 228:1615-1620, 1996; and Gopalakrishnan, V. et al. Endocrinology 123:922-930, 1988); gastrin (Peggion, E. et al. Biopolymers 23:1225-1240, 1984); glucagon (Epand, R. M. Mol. Pharmacol. 22:105-108, 1982; and Brimble, K. S. et al. Biochemistry 32:1632-164, 1993); GnRH (Gerega, K. et al. J. Inorg. Biochem. 33:11-18, 1988); insulin (Hill, C. P. et al. Biochemistry 30:917-924, 1991); substance P (Ananthanarayanan, V. S. et al. Biopolymers 32:1765-1773, 1992); and bombesin (Saint-Jean, A., et al., Poster presentation at the 13th American Peptide Symposium, Edmonton, Canada, 1993). The cell receptors of these hormones are also known to bind Ca.sup.2+ (Williams, P. F. et al. Cell Calcium 11:547-556, 1990. Synthetic peptide-metal complexes are potentially useful in methods for intracellular delivery of these cations.
To date, only two crystal structures of synthetic Ca.sup.2+ -complexes with peptides have been reported and both of these crystal structures are of cyclic peptides (Seetharama Jois, D. S. et al. Int. J. Peptide Protein Res. 41:484-491, 1993 and Varughese, K. I. et al. Int. J. Peptide Protein Res. 27:118-122, 1986. In c(Ala-Leu-Pro-Gly).sub.2.Ca(ClO.sub.4).sub.2 (Seetharama Jois, D. S. et al., 1993), complexation occurs through an incomplete encapsulation of the metal ion by the peptide molecule, and in c(Pro-Gly).sub.3.Ca(ClO.sub.4).sub.2 (Varughese, K. I. et al., 1986), a complete encapsulation is found wherein two cyclic peptide molecules sandwich a Ca.sup.2+ ion. Solvent molecules occupy coordination sites in both of these crystal structures. Complexation of linear peptides to Ca.sup.2+ cations in solution has been studied by a variety of techniques, such as CD, NMR, and IR spectroscopies. It is desirable to synthesize other types of linear metal-peptide complexes having biologically useful applications.